Avelumab in Non-Small Cell Lung Cancer (JAVELIN Lung 200)

Carcinoma, Non-Small-Cell Lung Clinical Trial

Official title:

A Phase III Open-Label, Multicenter Trial of Avelumab (MSB0010718C) Versus Docetaxel in Subjects With Non-Small Cell Lung Cancer That Has Progressed After a Platinum-Containing Doublet

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02395172
• Other study ID #: 100070-004
• Secondary ID: 2014-005060-15
• Status: Completed
• Phase: Phase 3
• Start date: March 24, 2015
• Est. completion date: December 3, 2019

Study information

• Verified date: July 2020
• Source: EMD Serono
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The main purpose of this study was to demonstrate superiority with regard to overall survival of avelumab versus docetaxel in participants with programmed death ligand 1 (PD-L1) positive, non-small cell lung cancer (NSCLC) after failure of a platinum-based doublet.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 792
• Est. completion date: December 3, 2019
• Est. primary completion date: November 22, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria

• Signed written informed consent before any trial related procedure

• Male or female participants aged greater than or equal to (>=) 18 years

• Availability of a formalin-fixed, paraffin-embedded block containing tumor tissue or 7 unstained tumor slides suitable for PD-L1 expression assessment

• Tumor determined to be evaluable for PD-L1 expression per the evaluation of a central laboratory

• Participants with histologically confirmed Stage IIIb/IV or recurrent NSCLC who have experienced disease progression

• Participants must have progressed after an acceptable therapy defined as follows:

1. Participants must have progressed during or after a minimum of 2 cycles of 1 course of a platinum based combination therapy administered for the treatment of a metastatic disease. A history of continuation (use of a non platinum agent from initial combination) or switch (use of a different agent) maintenance therapy is permitted provided there was no progression after the initial combination. A switch of agents during treatment for the management of toxicities is also permitted provided there was no progression after the initial combination OR

2. Participants must have progressed within 6 months of completion of a platinum-based adjuvant, neoadjuvant, or definitive chemotherapy, or concomitant chemoradiation regimen for locally advanced disease

• Participants with non-squamous cell NSCLC of unknown epidermal growth factor receptor (EGFR) mutation status will require testing (local laboratory, or central laboratory if local testing is not available). Participants with a tumor that harbors an activating EGFR mutation will not be eligible

• Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 to 1 at trial entry

• Estimated life expectancy of more than 12 weeks

• Adequate hematological function defined by White Blood Cell (WBC) count >= 2.5 × 10^9/L with absolute neutrophil count (ANC) >= 1.5 × 10^9/L, lymphocyte count >=0.5 × 10^9/L, platelet count >= 100 × 10^9/L, and hemoglobin >= 9 gram per deciliter (g/dL) (may have been transfused)

• Adequate hepatic function defined by a total bilirubin level less than or equal to (<=) 1.5 × the upper limit of normal (ULN) range and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels <= 2.5 × ULN for all participants

• Adequate renal function defined by an estimated creatinine clearance > 30 milliliter per minute (mL/min) according to the Cockcroft-Gault formula (or local institutional standard method).

Other protocol defined inclusion criteria could apply

Exclusion criteria

• In the United States only, participants with a squamous cell histology will be excluded

• Systemic anticancer therapy administered after disease progression during or following a platinum based combination

• Participants with non-squamous cell NSCLC whose disease harbors EGFR mutation(s) and/or anaplastic lymphoma kinase (ALK) rearrangement will not be eligible for this trial. Participants of unknown ALK and/or EGFR mutation status will require testing at screening (local laboratory, or central laboratory if local testing is not available)

• Prior therapy with any antibody/drug targeting T cell coregulatory proteins (immune checkpoints) such as PD-1, PD L1, or cytotoxic T lymphocyte antigen-4 (CTLA-4).

• Concurrent anticancer treatment

• Major surgery for any reason, except diagnostic biopsy, within 4 weeks of randomization and/or if the participant has not fully recovered from the surgery within 4 weeks of randomization

• Participants receiving immunosuppressive agents (such as steroids) for any reason should be tapered off these drugs before initiation of the trial treatment.

• All participants with brain metastases, except those meeting the following criteria:

1. Brain metastases have been treated locally, and

2. No ongoing neurological symptoms that are related to the brain localization of the disease

• Active autoimmune disease that might deteriorate when receiving an immunostimulatory agent:

1. Participants with diabetes type I, vitiligo, psoriasis, hypo- or hyperthyroid disease not requiring immunosuppressive treatment are eligible

2. Participants requiring hormone replacement with corticosteroids are eligible if the steroids are administered only for the purpose of hormonal replacement and at doses less than or equal to (<=)10 milligram (mg) or equivalent prednisone per day

3. Administration of steroids through a route known to result in a minimal systemic exposure are acceptable

• Previous or ongoing administration of systemic steroids for the management of an acute allergic phenomenon is acceptable as long as it is anticipated that the administration of steroids will be completed in 14 days, or that the daily dose after 14 days will be <=10 mg per day of equivalent prednisone

Other protocol defined exclusion criteria could apply

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms

Intervention

Drug:
• Avelumab
Participants received 10 milligrams per kilogram (mg/kg) of avelumab as a 1-hour intravenous infusion once every 2 weeks until confirmed disease progression, significant clinical deterioration, unacceptable toxicity, or any criterion for withdrawal from the study or Investigational Medicinal Product (IMP) as defined in the study protocol was fulfilled.
• Docetaxel
Participants received 75 mg per square meter (m^2) (per label) of docetaxel by intravenous infusion once every 3 weeks until confirmed disease progression, significant clinical deterioration, unacceptable toxicity, or any criterion for withdrawal from the study or Investigational Medicinal Product (IMP) as defined in the study protocol was fulfilled.

Locations

Country	Name	City	State
Argentina	Hospital Italiano Regional del Sur	Bahia Blanca
Argentina	Clínica Universitaria Privada Reina Fabiola	Barrio General Paz
Argentina	Centro de Oncologia e Investigacion Buenos Aires	Berazategui
Argentina	CEMIC	Ciudad Autonoma Buenos Aires
Argentina	Instituto Medico Especializado Alexander Fleming	Ciudad Autonoma Buenos Aires
Argentina	Instituto DAMIC Fundacion Rusculleda	Cordoba
Argentina	Centro Oncologico Riojano Integral (Cori)	La Rioja
Argentina	Centro Oncologico de Parana	Parana
Argentina	Hospital Universitario Austral	Pilar
Argentina	Instituto de Oncología de Rosario	Rosario
Argentina	Instituto Gamma	Rosario
Argentina	Sanatorio Parque S.A.	Rosario
Argentina	Centro Medico San Roque S.R.L.	San Miguel de Tucuman
Australia	Ballarat Base Hospital	Ballarat
Australia	Box Hill Hospital	Box Hill
Australia	Coffs Harbour Base Hospital	Coffs Harbour
Australia	Lyell McEwin Hospital	Elizabeth Vale
Australia	Greenslopes Private Hospital	Greenslopes
Australia	Lismore Base Hospital	Lismore
Australia	Royal Melbourne Hospital	Parkville
Australia	St John of God Hospital	Subiaco
Australia	Princess Alexandra Hospital	Woolloongabba
Belgium	UZ Antwerpen	Edegem
Belgium	Grand Hôpital de Charleroi	Gilly
Belgium	UZ Leuven	Leuven
Belgium	Centre Hospitalier de l'Ardenne	Libramont
Belgium	C. H. U. Sart Tilman	Liège
Belgium	AZ Delta	Roeselare
Brazil	Cenantron - Centro Avançado de Tratamento Oncológico S/C Ltda	Belo Horizonte
Brazil	CEPON - Centro de Pesquisas Oncológicas de Santa Catarina	Florianópolis
Brazil	Hospital de Caridade de Ijuí	Ijuí
Brazil	Clínica de Neoplasias Litoral Ltda.	Itajaí
Brazil	CMiP - Centro Mineiro de Pesquisa	Juiz de Fora
Brazil	Hospital Bruno Born	Lajeado
Brazil	Liga Norte-Rio-Grandense Contra o Câncer	Natal
Brazil	Oncosinos - Clínica de Oncologia - Hospital Regina	Novo Hamburgo
Brazil	CITO - Centro Integrado de Terapia Onco-Hematológica - Hospital da Cidade de Passo Fundo	Passo Fundo
Brazil	Hospital Mãe de Deus	Porto Alegre
Brazil	Hospital São Lucas da PUCRS	Porto Alegre
Brazil	COI - Clínicas Oncológicas Integradas	Rio de Janeiro
Brazil	CEPHO - Centro de Estudos e Pesquisas em Hematologia e Oncologia	Santo André
Brazil	Fundação Faculdade Regional de Medicina de São José do Rio Preto	São José do Rio Preto
Brazil	ICESP - Instituto do Câncer do Estado de São Paulo Octavio Frias de Oliveira	São Paulo
Brazil	IOS - Instituto de Oncologia de Sorocaba "Dr. Gilson Delgado"	Sorocaba
Bulgaria	UMHAT 'Dr. Georgi Stranski', EAD	Pleven
Bulgaria	Complex Oncological Center - Plovdiv, EOOD	Plovdiv
Bulgaria	MHAT "Serdika", EOOD	Sofia
Bulgaria	MHAT 'Tokuda Hospital Sofia', AD	Sofia
Bulgaria	Shato, Ead	Sofia
Bulgaria	MHAT 'Sv. Marina', EAD	Varna
Chile	CIEC - Centro Internacional de Estudios Clínicos	Santiago
Chile	FALP - Fundación Arturo López Pérez	Santiago
Chile	Instituto de Terapias Oncologicas Providencia	Santiago
Chile	Instituto Clinico Oncologico del Sur (ICOS)	Temuco
Chile	Centro de Investigaciones Clinicas Viña del Mar	Viña del Mar
Chile	Hospital Clinico Viña del Mar	Viña del Mar
Colombia	Clinica Colsanitas S.A. sede Clinica Universitaria Colombia	Bogota
Colombia	Fundacion Cardioinfantil Instituto de Cardiologia	Bogota
Colombia	Instituto Nacional de Cancerologia E.S.E.	Bogota
Colombia	Administradora Country S.A.	Bogotá
Colombia	Centro Medico Imbanaco	Cali
Colombia	Fundación Valle del Lilí	Cali
Colombia	Hemato Oncologos S.A.	Cali
Colombia	Instituto de Cancerologia S.A.	Medellin
Colombia	Hospital Pablo Tobón Uribe	Medellín
Colombia	IPS IMAT- Instituto Medico de Alta Tecnologia - Oncomedica S.A.	Monteria
Croatia	General Hospital Dubrovnik	Dubrovnik
Croatia	General Hospital Zadar	Zadar
Croatia	Clinical Hospital Centar "Sestre Milosrdnice"	Zagreb
Croatia	University Clinic for Pulmonary Diseases	Zagreb
Czechia	Masarykuv onkologicky ustav	Brno
Czechia	Nemocnice Novy Jicin a.s.	Novy Jicin
Czechia	Multiscan s.r.o.	Pardubice
Czechia	Vseobecna fakultni nemocnice V Praze	Praha 2
Czechia	Thomayerova nemocnice	Praha 4
Denmark	Herlev Hospital	Herlev
Denmark	Odense Universitetshospital	Odense C
France	ICO - Site Paul Papin	Angers Cedex 9
France	CHU Besançon - Hôpital Jean Minjoz	Besancon Cedex
France	Clinique Victor Hugo - Centre Jean Bernard	Le Mans Cedex 02
France	Hôpital Nord - AP-HM Marseille#	Marseille cedex 20
France	Centre Catherine de Sienne	Nantes
France	Centre Antoine Lacassagne	Nice cedex 02
France	Groupe Hospitalier Sud - Hôpital Haut-Lévêque	Pessac
France	CHU Poitiers - Hôpital la Milétrie	Poitiers
France	ICO - Site René Gauducheau	Saint Herblain
France	CHU Strasbourg - Nouvel Hôpital Civil	Strasbourg
France	CHU de Toulouse - Hôpital Larrey	Toulouse
Hungary	Semmelweis Egyetem AOK	Budapest
Hungary	Uzsoki Utcai Korhaz	Budapest
Hungary	Petz Aladar Megyei Oktato Korhaz	Györ
Hungary	Miskolci Semmelweis Korhaz es Egyetemi Oktatokorhaz	Miskolc
Hungary	Tudogyogyintezet Torokbalint	Torokbalint
Israel	Soroka Medical Center	Beer Sheva
Israel	Assaf Harofeh Medical Center	Beer Yaakov
Israel	Rambam Health Care Campus	Haifa
Israel	The Lady Davis Carmel Medical Center	Haifa
Israel	Hadassah University Hospital - Ein Kerem	Jerusalem
Israel	Sapir Medical Center, Meir Hospital	Kfar-Saba
Israel	Rabin Medical Center-Beilinson Campus	Petach Tikva
Israel	Chaim Sheba Medical Center	Ramat-Gan
Israel	Tel Aviv Sourasky Medical Center	Tel Aviv
Italy	Azienda Ospedaliera Istituti Ospitalieri di Cremona	Cremona
Italy	Ospedale Mater Salutis	Legnago (VR)
Italy	Ospedale Versilia	Lido di Camaiore
Italy	Fondazione IRCCS Istituto Nazionale dei Tumori	Milano
Italy	IEO Istituto Europeo di Oncologia	Milano
Italy	Seconda Università degli Studi di Napoli	Napoli
Italy	Azienda Ospedaliero Universitaria Pisana	Pisa
Italy	Azienda Ospedaliera Sant'Andrea-Università di Roma La Sapienza	Roma
Italy	Istituto Nazionale Tumori Regina Elena IRCCS	Roma
Italy	Policlinico Universitario Agostino Gemelli	Roma
Italy	Università Campus Bio-Medico di Roma	Roma
Italy	A.O.U. Senese Policlinico Santa Maria alle Scotte	Siena
Italy	Azienda Ospedaliera Ospedale Treviglio-Caravaggio di Treviglio	Treviglio
Japan	National Cancer Center Hospital	Chuo-ku
Japan	NHO Kyushu Cancer Center	Fukuoka-shi
Japan	Osaka Prefectural Medical Center for Respiratory and Allergic Diseases	Habikino-shi
Japan	Hiroshima City Hiroshima Citizens Hospital	Hiroshima-shi
Japan	National Cancer Center Hospital East	Kashiwa-shi
Japan	Saitama Cancer Center	Kitaadachi-gun
Japan	Institute of Biomedical Research and Innovation Hospital	Kobe-shi
Japan	Kobe City Hospital Organization Kobe City Medical Center General Hospital	Kobe-shi
Japan	Cancer Institute Hospital of JFCR	Koto-ku
Japan	Kurume University Hospital	Kurume-shi
Japan	Miyagi Cancer Center	Natori-shi
Japan	Aichi Cancer Center Hospital	Okazaki-shi
Japan	Osaka City General Hospital	Osaka-shi
Japan	Osaka Medical Center for Cancer and Cardiovascular Diseases	Osaka-shi
Japan	Kinki University Hospital	Osakasayama-shi
Japan	Kitasato University Hospital	Sagamihara-shi
Japan	Hokkaido University Hospital	Sapporo-shi
Japan	NHO Hokkaido Cancer Center	Sapporo-shi
Japan	Tokyo Medical University Hospital	Shinjuku-ku
Japan	Toyama University Hospital	Toyama-shi
Japan	Wakayama Medical University Hospital	Wakayama-shi
Japan	Kanagawa Cancer Center	Yokohama-shi
Japan	Yokohama Municipal Citizen's Hospital	Yokohama-shi
Korea, Republic of	Chungbuk National University Hospital	Cheongju-si
Korea, Republic of	Chonnam National University Hwasun Hospital	Hwasun-gun
Korea, Republic of	Gachon University Gil Medical Center	Incheon
Korea, Republic of	Seoul National University Bundang Hospital	Seongnam-si
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Korea University Anam Hospital	Seoul
Korea, Republic of	Korea University Guro Hospital	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	The Catholic University of Korea, Seoul St. Mary's Hospital	Seoul
Korea, Republic of	The Catholic University of Korea, St. Vincent's Hospital	Suwon-si
Mexico	Phylasis Clinicas Research S de RL de CV	Cuautitlan Izcalli
Mexico	Instituto de Investigaciones Aplicadas a la Neurociencia A.C.	Durango
Mexico	Fundacion Rodolfo Padilla Padilla, A.C.	Leon
Mexico	Health Pharma Professional Research S.A. de C.V.	Mexico
Mexico	Winsett Rethman S.A. de C.V.	Monterrey
Mexico	Centro de Investigacion Clinica Chapultepec S.A. de C.V.	Morelia
Mexico	Oaxaca Site Management Organization S.C.	Oaxaca
Mexico	Centro Oncologico Estatal ISSEMyM	Toluca
Peru	Clinica Monte Carmelo	Arequipa
Peru	Hospital Nacional Almanzor Aguinaga Asenjo	Chiclayo
Peru	Hospital Nacional Adolfo Guevara Velasco	Cusco
Peru	Clínica Ricardo Palma	Lima
Peru	Clinica San Borja	Lima
Peru	Hospital Nacional Guillermo Almenara Irigoyen	Lima
Peru	Instituto Nacional de Enfermedades Neoplásicas	Lima
Poland	Szpital Specjalistyczny W Brzozowie, Podkarpacki Osrodek Onkologiczny Im.Ks.B.Markiewicza	Brzozow
Poland	Wojewodzkie Centrum Szpitalne Kotliny Jeleniogorskiej	Jelenia Gora
Poland	Samodzielny Publiczny Szpital Kliniczny nr 5 SUM	Katowice
Poland	Centrum Terapii Wspolczesnej J.M. Jasnorzewska sp. komandytowo-akcyjna	Lodz
Poland	KO-MED Centra Kliniczne Lublin II	Lublin
Poland	SSZZOZ im. Dr Teodora Dunina w Rudce	Mrozy
Poland	Mazowieckie Centrum Leczenia Chorob Pluc i Gruzlicy	Otwock
Romania	Spitalul Judetean de Urgenta Alba Iulia	Alba Iulia
Romania	Spitalul Judetean de Urgenta "Dr. Constantin Opris" Baia Mare	Baia Mare
Romania	Policlinica de Diagnostic Rapid SRL	Brasov
Romania	Spitalul Clinic Municipal "Dr. Gavril Curteanu" Oradea	Oradea
Romania	Spital Lotus SRL	Ploiesti
Romania	S.C Oncocenter Oncologie Clinica S.R.L	Timisoara
Russian Federation	SHI "Republican Clinical Oncological Dispensary of HM RT"	Kazan
Russian Federation	SHBI Moscow Clinical Scientific Center of Department of Healthcare of Moscow	Moscow
Russian Federation	FSBHI Clinical research institute of phthisiopulmonology	Saint Petersburg
Russian Federation	Pavlov First Saint Petersburg State Medical University	Saint Petersburg
Russian Federation	FBI "Scientific Research Institute of Oncology n. a. N. N. Petrov"	St. Petersburg
Russian Federation	St. Petersburg SHI "City Clinical Oncology Dispensary"	St. Petersburg
Slovakia	Nemocnica s poliklinikou Sv. Jakuba, n.o. Bardejov	Bardejov
Slovakia	Univerzitna nemocnica Bratislava, Nemocnica Ruzinov	Bratislava
Slovakia	Ustredna vojenska nemocnica SNP Ruzomberok- Fakultna nemocnica	Ruzomberok
Slovakia	Fakultna nemocnica Trnava	Trnava
South Africa	GVI Cape Gate Oncology Centre	Cape Town
South Africa	GVI Rondebosch Oncology Centre	Cape town
South Africa	GVI Langenhoven Drive Oncology Centre	Port Elizabeth
South Africa	Mary Potter Oncology Centre	Pretoria
South Africa	University of Pretoria Oncology Department	Pretoria
Spain	Hospital General Universitario de Alicante	Alicante
Spain	ICO Badalona - Hospital Germans Trias i Pujol	Badalona
Spain	Hospital Clinic i Provincial de Barcelona	Barcelona
Spain	Hospital Universitari Quiron Dexeus	Barcelona
Spain	Hospital Universitari Vall d'Hebron	Barcelona
Spain	ICO l´Hospitalet - Hospital Duran i Reynals	L'Hospitalet de Llobregat
Spain	Hospital Universitario Materno-Infantil de Canarias	Las Palmas de Gran Canaria
Spain	Centro Integral Oncologico Clara Campal	Madrid
Spain	Hospital Universitario Ramon y Cajal	Madrid
Spain	Hospital Clinico Universitario Virgen de la Victoria	Malaga
Spain	Hospital de Mataro	Mataro
Spain	Complejo Hospitalario Universitario de Santiago	Santiago de Compostela
Spain	Hospital Universitario Virgen del Rocio	Sevilla
Spain	Hospital Universitario Virgen Macarena	Sevilla
Spain	Hospital Universitari i Politecnic La Fe	Valencia
Switzerland	Kantonsspital Graubuenden	Chur
Taiwan	Taichung Veterans General Hospital	Taichung
Taiwan	National Cheng Kung University Hospital	Tainan
Taiwan	National Taiwan University Hospital	Taipei
Taiwan	Taipei Veterans General Hospital	Taipei
Taiwan	Tri-Service General Hospital	Taipei
Taiwan	Chang Gung Memorial Hospital, Linkou	Taoyuan County
Turkey	Ankara University Medical Faculty	Ankara
Turkey	Baskent University Ankara Hospital	Ankara
Turkey	Hacettepe University Medical Faculty	Ankara
Turkey	Trakya University Medical Faculty	Edirne
Turkey	Bezmi Alem Foundation University Medical Faculty Hospital	Istanbul
Turkey	Fatih Universitesi Tip Fakultesi	Istanbul
Turkey	Istanbul University Cerrahpasa Medical Faculty	Istanbul
Turkey	Marmara University Pendik Research and Training Center	Istanbul
Turkey	Dokuz Eylul University Medicine Faculty	Izmir
Turkey	Ege University Medical Faculty	Izmir
Turkey	Konya Necmettin Erbakan University Meram Faculty of Medicine	Konya
United Kingdom	Royal Bournemouth General Hospital	Bournemouth
United Kingdom	Bristol Haematology & Oncology Centre	Bristol
United Kingdom	Royal Devon and Exeter Hospital (Wonford)	Exeter
United Kingdom	Beatson West of Scotland Cancer Centre	Glasgow
United Kingdom	St James's University Hospital	Leeds
United Kingdom	University College London Hospital	London
United Kingdom	Derriford Hospital	Plymouth
United Kingdom	Mount Vernon Hospital	Stevenage
United Kingdom	The Clatterbridge Cancer Centre	Wirral
United States	Abington Memorial Hospital	Abington	Pennsylvania
United States	Pacific Cancer Medical Center, Inc.	Anaheim	California
United States	Northeast Georgia Cancer Care, LLC	Athens	Georgia
United States	Lynn Cancer Institute Center	Boca Raton	Florida
United States	University Cancer Institute	Boynton Beach	Florida
United States	Oncology Hematology Care	Cincinnati	Ohio
United States	Henry Ford Health System	Detroit	Michigan
United States	Holy Cross Hospital Inc.	Fort Lauderdale	Florida
United States	Florida Cancer Specialists-Broadway	Fort Myers	Florida
United States	The Center for Cancer and Blood Disorders	Fort Worth	Texas
United States	Penn State Univ. Milton S. Hershey Medical Center	Hershey	Pennsylvania
United States	Center for Biomedical Research, LLC	Knoxville	Tennessee
United States	Healing Hands Oncology and Medical Care	Lawndale	California
United States	Metairie Oncologist, LLC	Metairie	Louisiana
United States	Signal Point Clinical Research Center	Middletown	Ohio
United States	Sutter Gould Medical Foundation	Modesto	California
United States	SCRI - Tennessee Oncology	Nashville	Tennessee
United States	Hematology Oncology Associates of Rockland	Nyack	New York
United States	Mercy Clinic Oklahoma Communities, Inc.	Oklahoma City	Oklahoma
United States	Florida Cancer Specialists	Saint Petersburg	Florida
United States	Sharp Memorial Hospital	San Diego	California
United States	Mayo Clinic	Scottsdale , Phoenix	Arizona
United States	MultiCare Health System	Tacoma	Washington
United States	University of Alabama	Tuscaloosa	Alabama
United States	University of Texas Health Science Center at Tyler	Tyler	Texas
United States	Florida Cancer Specialists	West Palm Beach	Florida
United States	Novant Health Oncology Specialists	Winston-Salem	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
EMD Serono Research & Development Institute, Inc.	Merck KGaA, Darmstadt, Germany

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Belgium,  Brazil,  Bulgaria,  Chile,  Colombia,  Croatia,  Czechia,  Denmark,  France,  Hungary,  Israel,  Italy,  Japan,  Korea, Republic of,  Mexico,  Peru,  Poland,  Romania,  Russian Federation,  Slovakia,  South Africa,  Spain,  Switzerland,  Taiwan,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival (OS) Time in Programmed Death Ligand 1 (PD-L1) + Full Analysis Set Population (FAS)	The OS time was defined as the time from randomization to the date of death. The participants who were still alive at the time of data analysis or who were lost to follow-up OS time was censored at the last recorded date that the participant was known to be alive before the data cutoff date. OS was measured using Kaplan-Meier (KM) estimates.	Time from date of randomization up to 1420 days
Secondary	Overall Survival (OS) Time in Full Analysis Set Population	The OS time was defined as the time from randomization to the date of death. The participants who were still alive at the time of data analysis or who were lost to follow-up OS time was censored at the last recorded date that the participant was known to be alive before the data cutoff date. OS was measured using Kaplan-Meier (KM) estimates.	Time from date of randomization up to 1420 days
Secondary	Progression-Free Survival (PFS) Time in PD-L1+ Full Analysis Set Population	PFS was defined as the time from date of randomization until date of the first documentation of progressive disease (PD) or death due to any cause in the absence of documented PD, whichever occurs first. PFS was assessed as per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) as adjudicated by independent endpoint review committee (IERC). PD was defined as at least a 20 percent (%) increase in the sum of longest diameter (SLD), taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions and unequivocal progression of non-target lesions. PFS was measured using Kaplan-Meier (KM) estimates.	Time from date of randomization up to 907 days
Secondary	Progression-Free Survival (PFS) Time in Full Analysis Set Population	PFS was defined as the time from date of randomization until date of the first documentation of progressive disease (PD) or death due to any cause in the absence of documented PD, whichever occurs first. PFS was assessed as per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) as adjudicated by independent endpoint review committee (IERC). PD was defined as at least a 20 percent (%) increase in the sum of longest diameter (SLD), taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions and unequivocal progression of non-target lesions. PFS was measured using Kaplan-Meier (KM) estimates.	Time from date of randomization up to 907 days
Secondary	Number of Participants With Confirmed Best Overall Response (BOR) as Assessed by an Independent Endpoint Review Committee (IERC) in Full Analysis Set Population	Confirmed BOR was determined according to RECIST v1.1 and as adjudicated by an IERC. Confirmed BOR was defined as the best response of any of the complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD) recorded from the date of randomization until disease progression or recurrence (taking the smallest measurement recorded since the start of treatment as reference). CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the sum of the longest diameter (SLD) of all lesions. SD: Neither sufficient increase to qualify for PD nor sufficient shrinkage to qualify for PR. PD was defined as at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions and unequivocal progression of non-target lesions. Number of participants with best overall response in each category (CR, PR, SD, PD) was reported.	Time from date of randomization up to 907 days
Secondary	Number of Participants With Confirmed Best Overall Response (BOR) as Assessed by Independent Endpoint Review Committee (IERC) in PD-L1+ Full Analysis Set Population	Confirmed BOR was determined according to RECIST v1.1 and as adjudicated by an IERC. Confirmed BOR was defined as the best response of any of the complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD) recorded from the date of randomization until disease progression or recurrence (taking the smallest measurement recorded since the start of treatment as reference). CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the sum of the longest diameter (SLD) of all lesions. SD: Neither sufficient increase to qualify for PD nor sufficient shrinkage to qualify for PR. PD was defined as at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions and unequivocal progression of non-target lesions. Number of participants with best overall response in each category (CR, PR, SD, PD) was reported.	Time from date of randomization up to 907 days
Secondary	Percentage of Participants With Objective Response as Assessed by Independent Endpoint Review Committee (IERC) in Full Analysis Set Population	Percentage of participants with objective response (CR plus PR) according to RECIST v1.1 was reported. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the sum of the longest diameter (SLD) of all lesions.	Time from date of randomization up to 907 days
Secondary	Percentage of Participants With Objective Response as Assessed by Independent Endpoint Review Committee (IERC) in PD-L1+ Full Analysis Set Population	Percentage of participants with objective response (CR plus PR) according to RECIST v1.1 was reported. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the sum of the longest diameter (SLD) of all lesions.	Time from date of randomization up to 907 days
Secondary	Change From Baseline in European Quality of Life 5-dimensions (EQ-5D-5L) Health Outcome Questionnaire Through Composite Index Score at End of Treatment (EOT)	The EQ-5D-5L health outcome questionnaire was a measure of health status that provides a simple descriptive profile and a single index value. The EQ-5D-5L defined health in terms of mobility, self-care, usual activities, pain/discomfort and anxiety/depression. The 5 items were combined to generate health profiles. These profiles were converted to a continuous single index score. The lowest possible score was -0.59 (unable to walk, unable to self-care, unable to do usual activities, extreme pain or discomfort, extreme anxiety or depression) and the highest was 1.00 (no problems in all 5 dimensions).	Baseline, End of treatment visit (up to Week 124)
Secondary	Change From Baseline in European Quality of Life 5-dimensions (EQ-5D-5L) Health Outcome Questionnaire Through Visual Analogue Scale (VAS) at End of Treatment (EOT)	EQ-5D-5L was comprised of the following 5 participant-reported dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension had 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. The responses were used to derive overall score using a visual analog scale (VAS) that ranged from 0 to 100 millimeter (mm), where 0 was the worst health you can imagine and 100 was the best health you can imagine.	Baseline, End of treatment visit (up to Week 124)
Secondary	Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life (EORTC QLQ-C30) Global Health Status at End of Treatment (EOT)	EORTC QLQ-C30 was a 30-question tool used to assess the overall quality of life (QoL) in cancer participants. It consisted of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, role, cognitive, emotional, social), and 9 symptom scales/items (Fatigue, nausea and vomiting, pain, dyspnea, sleep disturbance, appetite loss, constipation, diarrhea, financial impact). The EORTC QLQ-C30 GHS/QoL score ranged from 0 to 100; High score indicated better GHS/QoL. Score 0 represents: very poor physical condition and QoL. Score 100 represents: excellent overall physical condition and QoL.	Baseline, End of treatment visit (up to Week 124)
Secondary	Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer 13 (EORTC QLQ-LC13) at End of Treatment (EOT)	EORTC QLQ-LC13 consisted of 13 questions relating to disease symptoms specific to lung cancer and treatment side effects typical of treatment with chemotherapy and radiotherapy. The EORTC QLQ-LC13 module generated one multiple-item score assessing dyspnea and a series of single item scores assessing coughing, hemoptysis, sore mouth, dysphagia, neuropathy, alopecia, pain in chest, pain in arms or shoulder and pain in other parts. Score range: 0 (no burden of symptom domain or single symptom item) to 100 (highest burden of symptoms for symptom domains and single items).	Baseline, End of treatment visit (up to Week 124)
Secondary	Number of Participants With Treatment Emergent Adverse Events (TEAEs), Treatment Emergent Serious Adverse Events (TESAEs), Drug Related Treatment Emergent Adverse Events and Treatment Emergent Adverse Events Leading to Death	An Adverse event (AE) was defined as any unfavorable and unintended sign (including clinically significant abnormal laboratory, vital signs and 12-lead Electrocardiogram findings), symptom, or disease temporally associated with the use of study drug or worsening of pre-existing medical condition, whether or not related to study drug. A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. Treatment-emergent events were the events between first dose of study drug that were absent before treatment or that worsened relative to pre-treatment state up to 30 days after last administration. TEAEs included both Serious TEAEs and non-serious TEAEs.	Time from date of randomization up to 1420 days
Secondary	Number of Participants With Treatment Emergent Adverse Events (TEAEs) by Severity	Treatment Emergent Adverse Events were graded as per National Cancer Institute Common Terminology Criteria for Adverse Experience version 4.03 (NCI-CTCAE v 4.03). Grade 3 refers to severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care and Activity of daily living (ADL), Grade 4 refers to Life-threatening consequences; where urgent intervention indicated, Grade 5 refers to the death related to adverse event.	Time from date of randomization up to 1420 days
Secondary	Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score vs. Worst Post-baseline Score	ECOG performance status measured to assess participant's performance status on a scale of 0 to 5, where 0 = Fully active, able to carry on all pre-disease activities without restriction; 1 = Restricted in physically strenuous activity, ambulatory and able to carry out light or sedentary work; 2 = Ambulatory and capable of all selfcare but unable to carry out any work activities; 3 = Capable of only limited self-care, confined to bed/chair for more than 50 percent of waking hours; 4 = Completely disabled, cannot carry on any self-care, totally confined to bed/chair; 5 = dead. The participants with missing worst post baseline score were also reported. ECOG performance status was reported in terms of number of participants with Baseline value vs. worst post-baseline value (i.e. highest score) combination.	Time from date of randomization up to 1420 days
Secondary	Number of Participants With Positive Anti-Drug Antibodies (ADAs) and Neutralizing Antibodies (NAbs) for Avelumab	Serum samples were analyzed by a validated electrochemiluminesce immunoassay to detect the presence of antidrug antibodies (ADA). Samples that screened positive were subsequently tested in a confirmatory assay were tested for neutralizing antibodies (nAb). Number of participants with ADA or nAb positive results for Avelumab were reported.	Time from date of randomization up to 1420 days

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